The neuroactive compound, gamma-hydroxybutyrate (GHB), has been found to inhibit C-AMP formation in homogenates from rat rain. To determine in which cell type this effect occurs we have studied the influence of GHB on C-AMP formation in both neurons and astroglial cells in primary culture. In neurons the effect of GHB is to inhibit C-AMP formation whereas in the astroglial cells there is either no effect on stimulation of C-AMP formation. The effect of GHB on C-AMP formation reinforces the similarity between GHB and the opioid peptides. Work on the degradative pathway for GHB has continued. We are now able to estimate the contribution of the two enzymes, the cytosalic GHB-dehydrogenase and the mitochondrial hydroxyacid-oxoacid transhydrogenase, to the initial rate-limiting step in this pathway. Preparation of an antibody to the to the transhydrogenase will enable us to carry out precise localization of this new mitochondrial enzyme.